Fast-acting antimicrobial surfaces, and methods of making and using the same

ABSTRACT

An antimicrobial coating is disclosed that provides fast transport rates of biocides for better effectiveness to deactivate SARS-CoV-2 and other viruses or bacteria on common surfaces. Some variations provide an antimicrobial structure comprising: a solid structural phase comprising a solid structural material; a continuous transport phase that is interspersed within the solid structural phase, wherein the continuous transport phase comprises a solid transport material; and an antimicrobial agent contained within the continuous transport phase, wherein the solid structural phase and the continuous transport phase are separated by an average phase-separation length from about 100 nanometers to about 500 microns. The antimicrobial structure is capable of destroying at least 99.99 wt % of bacteria and/or viruses in 10 minutes of contact. Many options are disclosed for suitable materials to form the solid structural phase, the continuous transport phase, and the antimicrobial agent.

PRIORITY DATA

This patent application claims priority to U.S. Provisional Patent App.No. 63/037,921, filed on Jun. 11, 2020, which is hereby incorporated byreference herein.

FIELD OF THE INVENTION

The present invention generally relates to antimicrobial surfaces andcoatings, compositions suitable for antimicrobial surfaces and coatings,and methods of making and using the same.

BACKGROUND OF THE INVENTION

Coronavirus disease 2019 (“COVID-19”) is caused by severe acuterespiratory syndrome coronavirus 2 (“SARS-CoV-2”). The COVID-19 pandemichas emphasized the importance of environmental cleanliness and hygienemanagement involving a wide variety of surfaces. Despite the stricthygiene measures which have been enforced, it is has proven to be verydifficult to sanitize surfaces all of the time. Even when sanitized,surfaces may get contaminated again.

Respiratory secretions or droplets expelled by infected individuals cancontaminate surfaces and objects, creating fomites (contaminatedsurfaces). Viable SARS-CoV-2 virus can be found on contaminated surfacesfor periods ranging from hours to many days, depending on the ambientenvironment (including temperature and humidity) and the type ofsurface. See, for example, Van Doremalen et al., “Aerosol and surfacestability of SARS-CoV-2 as compared with SARS-CoV-1”, New EnglandJournal of Medicine 2020; 382: 1564-1567; Pastorino et al., “ProlongedInfectivity of SARS-CoV-2 in Fomites”, Emerging Infectious Diseases2020; 26(9); and Chin et al., “Stability of SARS-CoV-2 in differentenvironmental conditions”, The Lancet Microbe, e10, Apr. 2, 2020.

There is consistent evidence of SARS-CoV-2 contamination of surfaces andthe survival of the virus on certain surfaces. People who come intocontact with potentially infectious surfaces often also have closecontact with the infectious person, making the distinction betweenrespiratory droplet and fomite transmission difficult to discern.However, fomite transmission is considered a feasible mode oftransmission for SARS-CoV-2, given consistent findings aboutenvironmental contamination in the vicinity of infected cases and thefact that other coronaviruses and respiratory viruses can transmit thisway (World Health Organization, “Transmission of SARS-CoV-2:implications for infection prevention precautions”, Jul. 9, 2020 viawww.who.int). Virus transmission may also occur indirectly throughtouching surfaces in the immediate environment or objects contaminatedwith virus from an infected person, followed by touching the mouth,nose, or eyes. While use of face masks has, generally speaking, becomewidespread, use of hand gloves has not. Even with gloves, touching ofmouth, nose, and eyes still frequently occurs, following the touch of acontaminated surface.

Therefore, there is a desire to prevent the transmission of pathogens(such as, but not limited to, SARS-CoV-2) via surfaces. One method ofreducing pathogen transmission is to reduce the period of humanvulnerability to infection by reducing the period of viability ofSARS-CoV-2 on solids and surfaces.

Surfaces may be treated with chemical biocides, such as bleach andquaternary ammoniums salts, or UV light, to disinfect bacteria anddestroy viruses within a matter of minutes. Biocides in liquids arecapable of inactivating at least 99.99 wt % of SARS-CoV-2 in as littleas 2 minutes, which is attributed to the rapid diffusion of the biocideto microbes and because water aids microbial dismemberment. However,these approaches cannot always occur in real-time after a surface iscontaminated.

Alternatively, antimicrobial coatings may be applied to a surface inorder to kill bacteria and/or destroy viruses as they deposit. However,to exceed 99.9 wt % reduction of bacteria and/or viruses, conventionalantimicrobial coatings typically require at least 1 hour, a time scalewhich is longer than indirect human-to-human interaction time, such asin an aircraft or shared vehicle, for example. Existing solid coatingsare limited by a low concentration of biocides at the surface due toslow biocide transport. The slow diffusion of biocides through the solidcoating to the surface, competing with the removal of biocides from thesurface by human and environmental contact, results in limitedavailability and requires up to 2 hours to kill 99.9 wt % of bacteriaand/or deactivate 99.9 wt % of viruses.

Water improves transport and aids microbial dismemberment. However,single-material coatings have limited water uptake. Swelling with wateris often an unwanted characteristic of single-material coatings, sinceswelling which can cause coating weakness and degradation if notdesigned into the coating.

In view of the aforementioned needs in the art, there is a strong desirefor an antimicrobial coating that enables fast transport rates ofbiocides for better effectiveness on deactivating SARS-CoV-2 onsurfaces. The coating should be safe, conveniently applied orfabricated, and durable. It is particularly desirable for such a coatingto be capable of destroying at least 99 wt %, preferably at least 99.9wt %, and more preferably at least 99.99 wt % of bacteria and/or virusesin 30 minutes of contact, preferably 20 minutes of contact, and morepreferably 10 minutes of contact.

SUMMARY OF THE INVENTION

Some variations of the invention provide an antimicrobial structurecomprising:

(a) a solid structural phase comprising a solid structural material;

(b) a continuous transport phase that is interspersed within the solidstructural phase, wherein the continuous transport phase comprises asolid transport material; and

(c) an antimicrobial agent contained within the continuous transportphase,

wherein the solid structural phase and the continuous transport phaseare separated by an average phase-separation length from about 100nanometers to about 500 microns.

In some embodiments, the solid structural material is or includes asolid structural polymer selected from the group consisting of anon-fluorinated carbon-based polymer, a silicone, a fluorinated polymer,and combinations thereof.

A non-fluorinated carbon-based polymer may be selected from the groupconsisting of polyalkanes, polyurethanes, polyethers, polyureas,polyesters, and combinations thereof.

A silicone may be selected from the group consisting of polydimethylsiloxane, polytrifluoropropylmethyl siloxane, polyaminopropylmethylsiloxane, polyaminoethylaminopropylmethyl siloxane,polyaminoethylaminoisobutylmethyl siloxane, and combinations thereof.

A fluorinated polymer may be selected from the group consisting offluorinated polyols, perfluorocarbons, perfluoropolyethers,polyfluoroacrylates, polyfluorosiloxanes, polyvinylidene fluoride,polytrifluoroethylene, and combinations thereof.

In some embodiments, the solid transport material is or includes a solidtransport polymer selected from a hygroscopic polymer, a hydrophobic andnon-lipophobic polymer, a hydrophilic polymer, an electrolyte polymer,and combinations thereof.

A hygroscopic solid transport polymer may be selected from the groupconsisting of poly(acrylic acid), poly(ethylene glycol),poly(2-hydroxyethyl methacrylate), poly(vinyl imidazole),poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline),poly(vinylpyrolidone), modified cellulosic polymers, carboxymethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methylcellulose, and combinations thereof.

A hydrophobic, non-lipophobic solid transport polymer may be selectedfrom the group consisting of poly(propylene glycol), poly(tetramethyleneglycol), polybutadiene, polycarbonate, polycaprolactone, acrylicpolyols, and combinations thereof.

A hydrophilic solid transport polymer may be a polymer with ionic chargethat may be present within the hydrophilic solid transport polymer ascarboxylate groups, amine groups, sulfate groups, or phosphate groups,for example.

An electrolyte solid transport polymer may be selected from the groupconsisting of polyethylene oxide, polypropylene oxide, polycarbonates,polysiloxanes, polyvinylidene difluoride, and combinations thereof.

In preferred embodiments, the solid structural material is a solidstructural polymer, the solid transport material is a solid transportpolymer, and the solid structural polymer is crosslinked, via acrosslinking molecule, with the solid transport polymer. Thecrosslinking molecule may include at least one moiety selected from thegroup consisting of an amine moiety, a hydroxyl moiety, an isocyanatemoiety, and a combination thereof, for example. In certain embodiments,at least one moiety is an isocyanate moiety, which may be a blockedisocyanate.

In some embodiments, the continuous transport phase is a solid solutionor solid suspension of the solid transport material and theantimicrobial agent.

In other embodiments, the continuous transport phase contains atransport-phase liquid that at least partially dissolves theantimicrobial agent. The transport-phase liquid may be selected from thegroup consisting of water, dialkyl carbonate, propylene carbonate,γ-butyrolactone, 2-phenoxyethanol, and combinations thereof.

Alternatively, or additionally, the transport-phase liquid is selectedfrom polar solvents.

Alternatively, or additionally, the transport-phase liquid is selectedfrom ionic liquids.

In certain embodiments, the transport-phase liquid contains one or morewater-soluble salts, one or more of which may function as anantimicrobial agent. Exemplary water-soluble salts include, but are notlimited to, copper chloride, copper nitrate, zinc chloride, zincnitrate, silver chloride, silver nitrate, or combinations thereof. Insome embodiments, water-soluble salts are selected from quaternaryammonium salts, such as benzalkonium chloride, benzethonium chloride,methylbenzethonium chloride, cetalkonium chloride, cetylpyridiniumchloride, cetrimonium, cetrimide, tetraethylammonium bromide,didecyldimethylammonium chloride, dioctyldimethylammonium chloride,domiphen bromide, or combinations thereof.

In certain embodiments, the transport-phase liquid is a eutectic liquidsalt, which is optionally derived from ammonium salts. The eutecticliquid salt may contain an antimicrobial agent or be otherwiseantimicrobially active.

In some embodiments, the continuous transport phase contains a liquidelectrolyte, a solid electrolyte, or both a liquid electrolyte and asolid electrolyte.

In some embodiments, the antimicrobial agent is selected from quaternaryammonium molecules. Exemplary quaternary ammonium molecules include, butare not limited to, benzalkonium chloride, benzethonium chloride,methylbenzethonium chloride, cetalkonium chloride, cetylpyridiniumchloride, cetrimonium, cetrimide, tetraethylammonium bromide,didecyldimethylammonium chloride, dioctyldimethylammonium chloride, anddomiphen bromide.

In some embodiments, the antimicrobial agent is selected fromN-halamines. Exemplary N-halamines include, but are not limited to,hydantoin (imidazolidine-2,4-dione); 1,3-dichloro-5,5-dimethylhydantoin;3-bromo-1-chloro-5,5-dimethylhydantoin; 5,5-dimethylhydantoin;4,4-dimethyl-2-oxazalidinone; tetramethyl-2-imidazolidinone; and2,2,5,5-tetramethylimidazo-lidin-4-one.

In some embodiments, the antimicrobial agent is selected from oxidizingmolecules, such as (but not limited to) those selected from the groupconsisting of sodium hypochlorite, hypochlorous acid, hydrogen peroxide,and combinations thereof.

In some embodiments, the antimicrobial agent is selected from metalions, such as (but not limited to) metal ions selected from the groupconsisting of silver, copper, zinc, and combinations thereof.

The antimicrobial structure may be characterized in that theantimicrobial agent has a diffusion coefficient between 10⁻¹⁶ m²/s and10⁻⁹ m²/s, measured at 25° C. and 1 bar, within the continuous transportphase.

The antimicrobial structure may be characterized in that theantimicrobial agent is replenished on an outer surface of theantimicrobial structure to at least 25% of the original concentration ofantimicrobial agent, in 100 minutes or less.

In some embodiments, the antimicrobial structure contains embeddedelectrodes in a configuration such that the antimicrobial agent iselectrically or electrochemically rechargeable.

The antimicrobial structure may further contain one or more additives,such as (but not limited to) salts, buffers, UV stabilizers, fillers, orcombinations thereof.

The antimicrobial structure may further contain one or more protectivelayers, such as environmentally protective layer(s).

In some antimicrobial structures, the average phase-separation length isfrom about 0.5 microns to about 100 microns. In certain embodiments, theaverage phase-separation length is from about 1 micron to about 50microns.

The antimicrobial structure may be a coating or may be present in acoating. Alternatively, or additionally, the antimicrobial structure maybe present at a surface of a bulk object. The antimicrobial structuremay be the entirety of a bulk object.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top view of an antimicrobial structure that contains adiscrete solid phase that provides abrasion resistance, and a continuoustransport phase that transports antimicrobial agents to the outersurface to inactivate or kill microbes, in some embodiments of theinvention.

FIG. 2 is a through-thickness side view of a coating or bulk materialthat contains a discrete solid phase and a continuous transport phasethat stores antimicrobial agents and transports the antimicrobial agentsto the outer layer in order to inactivate or kill microbes, in someembodiments.

FIG. 3 is a sketch of an antimicrobial structure (through-thickness sideview) with an antimicrobial agent that is rechargeable by applying avoltage between two embedded electrodes of opposite polarity, in someembodiments of the invention.

FIG. 4 shows the magnitude of impedance for six poly(ethyleneglycol)-polyTHF films with various PEG concentrations after immersion ina 10% benzalkonium chloride solution, in Example 3.

FIG. 5 shows a plot of specific conductivity and diffusion coefficientsof poly(ethylene glycol)-polyTHF films as a function of PEGconcentration after immersion in a 10% benzalkonium chloride solution,in Example 3.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The structures, systems, compositions, and methods of the presentinvention will be described in detail by reference to variousnon-limiting embodiments.

This description will enable one skilled in the art to make and use theinvention, and it describes several embodiments, adaptations,variations, alternatives, and uses of the invention. These and otherembodiments, features, and advantages of the present invention willbecome more apparent to those skilled in the art when taken withreference to the following detailed description of the invention inconjunction with the accompanying drawings.

As used in this specification and the appended claims, the singularforms “a,” “an,” and “the” include plural referents unless the contextclearly indicates otherwise. Unless defined otherwise, all technical andscientific terms used herein have the same meaning as is commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs.

Unless otherwise indicated, all numbers expressing conditions,concentrations, dimensions, and so forth used in the specification andclaims are to be understood as being modified in all instances by theterm “about.” Accordingly, unless indicated to the contrary, thenumerical parameters set forth in the following specification andattached claims are approximations that may vary depending at least upona specific analytical technique.

The term “comprising,” which is synonymous with “including,”“containing,” or “characterized by” is inclusive or open-ended and doesnot exclude additional, unrecited elements or method steps. “Comprising”is a term of art used in claim language which means that the named claimelements are essential, but other claim elements may be added and stillform a construct within the scope of the claim.

As used herein, the phrase “consisting of” excludes any element, step,or ingredient not specified in the claim. When the phrase “consists of”(or variations thereof) appears in a clause of the body of a claim,rather than immediately following the preamble, it limits only theelement set forth in that clause; other elements are not excluded fromthe claim as a whole. As used herein, the phrase “consisting essentiallyof” limits the scope of a claim to the specified elements or methodsteps, plus those that do not materially affect the basis and novelcharacteristic(s) of the claimed subject matter.

With respect to the terms “comprising,” “consisting of,” and “consistingessentially of,” where one of these three terms is used herein, thepresently disclosed and claimed subject matter may include the use ofeither of the other two terms, except when used in a Markush group. Thusin some embodiments not otherwise explicitly recited, any instance of“comprising” may be replaced by “consisting of” or, alternatively, by“consisting essentially of.”

Some variations of the invention are predicated on polymeric coatingsthat are solid but have fast transport rates of antimicrobial agents,enabled by a two-phase architecture with a solid structural phasecombined with an antimicrobial-containing continuous transport phasethat is phase-separated with the solid structural phase. As defined inthis patent application, “antimicrobial agents” or synonymously“antimicrobial actives” include germicides, bactericides, virucides(antivirals), antifungals, antiprotozoals, antiparasites, and biocides.In some embodiments, antimicrobial agents are specifically bactericides,such as disinfectants, antiseptics, and/or antibiotics. In someembodiments, antimicrobial agents are specifically virucides, or includevirucides.

This invention resolves the technical tradeoffs between antimicrobialsolutions and solid surfaces. Conventional liquid solutions are fast butnot persistent. Liquid solutions can reduce the population of bacteriaand viruses on a timescale of minutes, but the liquid solutions do notstay on surfaces and have a one-time effect. Conventional solidantimicrobial surfaces reduce bacteria and virus populations quiteslowly, causing bacteria and virus to remain on surfaces for extendedtimes. See Behzadinasab et al., “A Surface Coating that RapidlyInactivates SARS-CoV-2”, ACS Appl. Mater. Interfaces 2020, 12, 31, as anexample of an antimicrobial coating that requires at least 1 hour foreffectiveness. The slow activity of conventional solid antimicrobialmaterials is due to the time needed for antimicrobial agents to diffuseto the surface. These surfaces also fail to work if they are dirty,because soil blocks the transport of antimicrobial agents to thesurface.

By contrast, the material disclosed herein breaks the trade betweenactivity and persistence. The solid structural phase providespersistence on a surface while the continuous transport phase allowsantimicrobial agents to move to microbes (e.g., viruses or bacteria) onthe surface at order-of-magnitude faster rates than is possible withdiffusion through a single solid material. A biphasic structuresimultaneously provides durability and fast transport to the surfacewhere antimicrobial agents can kill or deactivate microbes at thesurface. The continuous transport phase may contain an aqueous ornon-aqueous solvent or electrolyte to further enhance transport rates ofantimicrobial agents. In some embodiments, the continuous transportphase passively absorbs water from the environment, which water mayenhance transport rates of antimicrobial agents and/or improve theeffectiveness of the antimicrobial agents.

There are many commercial applications of antimicrobial surfaces inhomes (e.g., kitchens and bathrooms), in restaurants, on clothing andpersonal protective equipment, in cars (especially shared-ride vehiclesto inhibit the transfer of microbes from one person to another), inairplanes (e.g., for contaminated surfaces that UV light cannot reach),and inside and outside vehicles used to rescue or move people who havebeen exposed to diseases and pandemics.

Some variations of the invention provide an antimicrobial structurecomprising:

(a) a solid structural phase comprising a solid structural material;

(b) a continuous transport phase that is interspersed within the solidstructural phase, wherein the continuous transport phase comprises asolid transport material; and

(c) an antimicrobial agent contained within the continuous transportphase,

wherein the solid structural phase and the continuous transport phaseare separated by an average phase-separation length from about 100nanometers to about 500 microns.

Certain variations provide an antimicrobial structure intended tocontain antimicrobial agent, the antimicrobial structure comprising:

(a) a solid structural phase comprising a solid structural material;

(b) a continuous transport phase that is interspersed within the solidstructural phase, wherein the continuous transport phase comprises asolid transport material, and wherein the continuous transport phase iscapable of containing an antimicrobial agent (such as at a time ofintended use or regeneration),

wherein the solid structural phase and the continuous transport phaseare separated by an average phase-separation length from about 100nanometers to about 500 microns.

In some embodiments, the solid structural material is or includes asolid structural polymer selected from the group consisting of anon-fluorinated carbon-based polymer, a silicone, a fluorinated polymer,and combinations thereof. These types of polymers are preferred whenanti-wetting properties (from water or other hydrophilic liquids) aredesired for the solid structural material, providing a dry-feel surface.A hydrophobic and/or lyophobic solid structural material prevents orminimizes soil adhesion and penetration of debris into the overallstructure.

A non-fluorinated carbon-based polymer may be selected from the groupconsisting of polyalkanes, polyurethanes, polyethers, polyureas,polyesters, and combinations thereof.

A silicone may be selected from the group consisting of polydimethylsiloxane, polytrifluoropropylmethyl siloxane, polyaminopropylmethylsiloxane, polyaminoethylaminopropylmethyl siloxane,polyaminoethylaminoisobutylmethyl siloxane, and combinations thereof.

A fluorinated polymer may be selected from the group consisting offluorinated polyols, perfluorocarbons, perfluoropolyethers,polyfluoroacrylates, polyfluorosiloxanes, polyvinylidene fluoride,polytrifluoroethylene, and combinations thereof.

In some embodiments, the solid transport material is or includes a solidtransport polymer selected from a hygroscopic polymer, a hydrophobic andnon-lipophobic polymer, a hydrophilic polymer, an electrolyte polymer,and combinations thereof. As described below, the continuous transportphase may further include a transport-phase liquid, which may be organicor inorganic.

In some embodiments, the solid transport material is or includes ahygroscopic solid transport polymer. The hygroscopic solid transportpolymer may be selected from the group consisting of poly(acrylic acid),poly(ethylene glycol), poly(2-hydroxyethyl methacrylate), poly(vinylimidazole), poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline),poly(vinylpyrolidone), modified cellulosic polymers, carboxymethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methylcellulose, and combinations thereof, for example. For instance, ahygroscopic solid transport polymer may be a crosslinked poly(acrylicacid) emulsion polymer (e.g., Carbopol® polymers) that can bind withantimicrobial agents.

In some embodiments, the solid transport material is or includes ahydrophobic, non-lipophobic solid transport polymer. The hydrophobic,non-lipophobic solid transport polymer may be selected from the groupconsisting of poly(propylene glycol) (PPG), poly(tetramethylene glycol)(PTMEG, also known as polytetrahydrofuran or polyTHF), polybutadiene,polycarbonate, polycaprolactone, acrylic polyols, and combinationsthereof, for example.

In some embodiments, the solid transport material is or includes ahydrophilic solid transport polymer. The hydrophilic solid transportpolymer may be a polymer created with ionic charge that may be presentwithin the hydrophilic solid transport polymer as pendant or main-chaincarboxylate groups, amine groups, sulfate groups, or phosphate groups,for example. In certain embodiments, monomers containing ionic chargeare inserted along the polymer backbone. The hydrophilic solid transportpolymer may bind with antimicrobial agents.

In some embodiments, the solid transport material is or includes anelectrolyte solid transport polymer. The electrolyte solid transportpolymer may be selected from the group consisting of polyethylene oxide,polypropylene oxide, polycarbonates, polysiloxanes, polyvinylidenedifluoride, and combinations thereof, for example.

In preferred embodiments, a solid structural polymer is crosslinked, viaa crosslinking molecule, with a solid transport polymer. Thecrosslinking is preferably covalent crosslinking, but can also be ioniccrosslinking. When the discrete and continuous phases are covalentlycrosslinked, an abrasion-resistant structure is established within thecontinuous transport phase. Additionally, when the structural polymerand the transport polymer are crosslinked, the length scales of thedifferent phases can be controlled, such as to enhance transport ratesof the antimicrobial agent.

A crosslinking molecule (when present) may include at least one moietyselected from the group consisting of an amine moiety, a hydroxylmoiety, an isocyanate moiety, and a combination thereof, for example.Other crosslinking molecules may be employed. In certain embodiments, atleast one moiety is an isocyanate moiety, which may be a blockedisocyanate.

In some embodiments, the continuous transport phase is a solid solutionor solid suspension of the solid transport material and theantimicrobial agent. For example, when the antimicrobial agent is aliquid, the continuous transport phase may be a solution of the solidtransport material and the antimicrobial agent. When the antimicrobialagent is a solid, the continuous transport phase may be a suspension ofthe solid transport material and the antimicrobial agent.

In other embodiments, the continuous transport phase contains atransport-phase liquid that at least partially dissolves theantimicrobial agent. The transport-phase liquid may be selected from thegroup consisting of water, dialkyl carbonate, propylene carbonate,γ-butyrolactone, 2-phenoxyethanol, and combinations thereof.

Alternatively, or additionally, the transport-phase liquid is selectedfrom polar solvents. Polar solvents may be protic polar solvents oraprotic polar solvents. Exemplary polar solvents include, but are notlimited to, water, alcohols, ethers, esters, ketones, aldehydes,carbonates, and combinations thereof. In some embodiments, thetransport-phase liquid is water that is passively incorporated fromatmospheric humidity.

Alternatively, or additionally, the transport-phase liquid is selectedfrom ionic liquids. Exemplary ionic liquids include, but are not limitedto, ammonium-based ionic liquids synthesized from substituted quaternaryammonium salts.

The transport-phase liquid may include a high ion concentration to aidtransport of antimicrobial agent and/or to enhance the uptake of fluidsthat, in turn, aid transport of antimicrobial agent.

In some embodiments, the antimicrobial agent is selected from quaternaryammonium molecules (whether or not classified as an ionic liquid).Exemplary quaternary ammonium molecules include, but are not limited to,benzalkonium chloride, benzethonium chloride, methylbenzethoniumchloride, cetalkonium chloride, cetylpyridinium chloride, cetrimonium,cetrimide, tetraethylammonium bromide, didecyldimethylammonium chloride,dioctyldimethylammonium chloride, and domiphen bromide. Quaternaryammonium molecules or eutectic mixtures of quaternary ammonium moleculesthat are liquids at room temperature—ionic liquids or ionic liquideutectics, respectively—enable liquid-state rates of transport withnegligible vapor pressure. A specific example is tetrabutylammoniumheptadecafluorooctanesulfonate (C₂₄H₃₆F₁₇NO₃S), which has a meltingpoint <5° C. Another specific example is tetraoctylammonium chloride(C₃₂H₆₈ClN) with a melting point of 50-54° C. mixed withtetraheptylammonium chloride (C₂₈H₆₀ClN) with a melting point of 38-41°C. in a eutectic composition ratio that forms a liquid at roomtemperature (25° C.). Quaternary ammonium molecules may be mixed withimidazolium-based ionic liquids, pyridinium-based ionic liquids,pyrrolidinium-based ionic liquids, and/or phosphonium-based ionicliquids.

In certain embodiments, the transport-phase liquid contains one or morewater-soluble salts, one or more of which may function as anantimicrobial agent. Exemplary water-soluble salts include, but are notlimited to, copper chloride, copper nitrate, zinc chloride, zincnitrate, silver chloride, silver nitrate, or combinations thereof. Otherexemplary water-soluble salts include quaternary ammonium salts, such as(but not limited to) the quaternary ammonium molecules recited above.

In certain embodiments, the transport-phase liquid is a eutectic liquidsalt, which is optionally derived from ammonium salts. The eutecticliquid salt may contain an antimicrobial agent or be otherwiseantimicrobially active.

In some embodiments, the antimicrobial agent is selected fromN-halamines. N-halamines are compounds that stabilize an oxidizing agent(such as chlorine contained within the N-halamine molecule) and may beused to kill or deactivate microbes. N-halamines remain stable, unlikesodium hypochlorite (bleach), over long time periods and may berecharged by exposure to an oxidizer such as dilute bleach or ozone.Exemplary N-halamines include, but are not limited to, hydantoin(imidazolidine-2,4-dione); 1,3-dichloro-5,5-dimethylhydantoin;3-bromo-1-chloro-5,5-dimethylhydantoin; 5,5-dimethylhydantoin;4,4-dimethyl-2-oxazalidinone; tetramethyl-2-imidazolidinone; and2,2,5,5-tetramethylimidazo-lidin-4-one. Examples of antimicrobialN-halamines are also disclosed in Lauten et al., Applied andEnvironmental Microbiology Vol. 58, No. 4, Pages 1240-1243 (1992), whichis incorporated by reference.

In some embodiments, the antimicrobial agent is selected from oxidizingmolecules, such as (but not limited to) those selected from the groupconsisting of sodium hypochlorite, hypochlorous acid, hydrogen peroxide,and combinations thereof.

In some embodiments, the antimicrobial agent is selected from metalions, such as (but not limited to) silver, copper, zinc, cobalt, nickel,or combinations thereof. Any metal ion with at least some antimicrobialactivity itself, or which confers antimicrobial activity to a compoundwhich the metal ion binds to, may be employed. The metal ion may bepresent in a metal complex or a metal salt, for example. In certainembodiments, the antimicrobial agent contains a neutral metal (e.g.,zero-valent silver, copper, or zinc) which may be dissolved in a liquidand/or may be present as nanoparticles, for example.

A liquid electrolyte or solid electrolyte (or both) may be included inthe continuous transport phase, to increase transport rates of theantimicrobial agent.

An exemplary electrolyte is a complex formed between poly(ethyleneoxide) and metal salts, such as poly(ethylene oxide)-Cu(CF₃SO₃)₂ whichis a known copper conductor. Cu(CF₃SO₃)₂ is the copper(II) salt oftrifluoromethanesulfonic acid. See Bonino et al., “Electrochemicalproperties of copper-based polymer electrolytes”, Electrochimica Acta,Vol. 37, No. 9, Pages 1711-1713 (1992), which is incorporated byreference.

When a liquid electrolyte is included in the continuous transport phase,one or more solvents for the liquid electrolyte may be present. Solventsfor the liquid electrolyte may be selected from the group consisting ofsulfoxide, sulfolane, ethylene carbonate, propylene carbonate, dimethylcarbonate, diethyl carbonate, methyl ethyl carbonate,1,2-dimethoxyethane, 1,2-diethoxyethane, γ-buterolactone,γ-valerolactone, 1,3-dioxolane, tetrahydrofuran,2-methyltetrahydrofuran, acetonitrile, proprionitrile, diglyme,triglyme, methyl formate, trimethyl phosphate, triethyl phosphate, andmixtures thereof, for example.

When a liquid electrolyte is included in the continuous transport phase,there may be a salt within an aqueous or non-aqueous solvent. Exemplarysalts are salts of transition metals (e.g., V, Ti, Cr, Co, Ni, Cu, Zn,Tb, W, Ag, Cd, or Au), salts of metalloids (e.g., Al, Ga, Ge, As, Se,Sn, Sb, Te, or Bi), salts of alkali metals (e.g., Li, Na, or K), saltsof alkaline earth metals (e.g., Mg or Ca), or a combination thereof.

In some embodiments, a gel electrolyte is included in the continuoustransport phase. A gel electrolyte contains a liquid electrolyteincluding an aqueous or non-aqueous solvent as well as a salt, in apolymer host. The solvent and salt may be selected from the lists above.The polymer host may be selected from the group consisting ofpoly(ethylene oxide), poly(vinylidene fluoride), poly(acrylonitrile),poly(methyl methacrylate), poly(vinylidene fluoride-hexafluoropropylene)(PVdF-co-HFP, polycarbonate, polysiloxane, and combinations thereof.

When a solid electrolyte is included in the continuous transport phase,the solid electrolyte is preferably concentrated enough to enablesufficient ionic percolation. Solid electrolytes may be oxides,sulfides, halides, or a combination thereof. Exemplary solidelectrolytes include, but are not limited to, β-alumina, β″-alumina,Cu-β-alumina, Cu-β″-alumina, Ag-β-alumina, and Ag-β″-alumina. β-aluminaand β″-alumina are good conductors of mobile ions. β″-alumina is a hardpolycrystalline or monocrystalline ceramic which, when prepared as anelectrolyte, is complexed with a mobile ion, such as (but not limitedto) Cu²⁺ or Ag⁺. β-alumina and/or β″-alumina are also referred to hereinas “beta-alumina.”

Other solid electrolytes include yttria-stabilized zirconia, sodiumsuperionic conductor (NASICON), lithium superionic conductor (LISICON),potassium superionic conductor (KSICON), lithium thiogermanatethiophosphate (LGPS), or combinations of any of the foregoing.Chalcogenide glasses may be used as solid electrolytes. Exemplarychalcogenide glasses include RbI—GeSe₂—Ga₂Ge₃ and CsI—GeSe₂—Ga₂Ge₃.

Solid electrolytes for conducting copper ions may include cuproushalides, such as (but not limited to) CuCl, CuBr, CuI, or a combinationthereof. Conductivities on the order of 0.1 S/cm are possible at roomtemperature with some mixed phases, such as RbCuClI. Solid electrolytesfor conducting copper ions may include copper sulfides, Cu_(x)S_(y),wherein x and y may vary. For example, when y=1, x may be selected fromabout 1 to less than 2, such as 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7,1.8, or 1.9.

Solid electrolytes for conducting silver ions may include silver-ionconductors, such as (but not limited to) AgI, Ag₂SeO₄, RbAg₄I₅, or acombination thereof. AgI has an ionic conductivity of about 0.1 S/cm at150° C. RbAg₄I₅ has an ionic conductivity of about 0.1 S/cm at 25° C.

When a solid electrolyte is present, it may be incorporated into thecontinuous transport phase as its own continuous or semi-continuousphase, meaning that there is physical connectivity of regions of solidelectrolyte. However, the solid electrolyte need not be continuousthroughout the entire material. In certain embodiments, the solidelectrolyte is incorporated into a solid matrix phase that is distinctfrom the continuous transport phase. In these embodiments, the separatesolid electrolyte matrix phase may be polymeric, ceramic, metallic, or acombination thereof.

In certain embodiments, the antimicrobial structure further contains oneor more layers of an antimicrobial-agent storage phase that is distinctfrom the continuous transport phase and the solid structural phase. Inthese or other certain embodiments, the antimicrobial structure furthercontains inclusions of an antimicrobial-agent storage phase that isdistinct from the continuous transport phase and the solid structuralphase. An antimicrobial-agent storage phase may be fabricated from thesame material as the solid transport material, or from a differentmaterial. For example, both the solid transport material and theantimicrobial-agent storage phase (when present) may be made from ahydrophobic, non-lipophobic polymer. The antimicrobial-agent storagephase may contain an antimicrobial agent that is released initially,continuously, or periodically into the continuous transport phase.

The antimicrobial structure may further contain one or more additives,such as (but not limited to) salts, buffers, UV stabilizers, fillers, orcombinations thereof. Additives, when present, may be incorporated intothe solid structural phase, the continuous transport phase, both ofthese phases, or neither of these phases but within a separate phase.

When an additive is a salt, there will be a cation and anion forming thesalt. The cation element may be Li, Na, K, Mg, and/or Ca, for example.The anion element or group may be F, Cl, Br, I, SO₃, SO₄, NO₂, NO₃,CH₃COO, and/or CO₃, for example.

When an additive is a buffer, it may be an inorganic or organic moleculethat maintains a pH value or pH range via acid-base reactions. A buffermay be discrete or may be bonded to the solid transport material, forexample.

When an additive is a UV stabilizer, it may be an antioxidant (e.g., athiol), a hindered amine (e.g., a derivative of tetramethylpiperidine),UV-absorbing nanoparticles (e.g., CdS, CdTe, or ZnS—Ag nanoparticles),or a combination thereof, for example.

When an additive is a particulate filler, it may be selected from thegroup consisting of silica, alumina, silicates, talc, aluminosilicates,barium sulfate, mica, diatomite, calcium carbonate, calcium sulfate,carbon, wollastonite, and a combination thereof, for example. Aparticulate filler is optionally surface-modified with a compoundselected from the group consisting of fatty acids, silanes,alkylsilanes, fluoroalkylsilanes, silicones, alkyl phosphonates, alkylphosphonic acids, alkyl carboxylates, alkyldisilazanes, and combinationsthereof, for example.

An exemplary antimicrobial structure 100 is depicted in FIG. 1, which isa top view of the outer surface of the antimicrobial structure 100. InFIG. 1, the antimicrobial structure 100 is biphasic, containing adiscrete solid phase 110 that provides abrasion resistance, and acontinuous transport phase 120 that stores antimicrobial agents andtransports the antimicrobial agents to the outer surface in order toinactivate or kill microbes. An antimicrobial agent (not shown) ispreferably contained selectively within the continuous transport phase120, such that the antimicrobial structure 100 is capable of destroyingmicrobes (e.g., viruses and/or bacteria). The 100-micron scale bar inFIG. 1 is exemplary and indicative of the length scales of the discretesolid phase 110, the continuous transport phase 120, and the distancebetween the phases. The structure 100 may be a coating on a substrate(not shown) or may be a bulk material or object, for example.

An exemplary antimicrobial structure 200 is depicted in FIG. 2, which isa through-thickness side view of a coating or bulk material. There is anouter layer 250 that may contain microbes from environmental sources(microbes not depicted) and is generally exposed to the environment. InFIG. 2, the antimicrobial structure 200 is biphasic, containing adiscrete solid phase 210 and a continuous transport phase 220 thatstores antimicrobial agents and transports the antimicrobial agents tothe outer layer 250 in order to inactivate or kill microbes that may bepresent there. An antimicrobial agent (not shown) is preferablycontained selectively within the continuous transport phase 220, suchthat the antimicrobial structure 200 is capable of destroying microbes(e.g., viruses and/or bacteria) after transport of the antimicrobialagent to the outer layer 250 and/or potentially after diffusion ofmicrobes from the outer layer 250 into the continuous transport phase220 which exposes the microbes to the antimicrobial agent. The structure200 may be a coating on a substrate (not shown) or may be a bulkmaterial or object, for example. A substrate, if present, wouldtypically be distally opposite the outer layer 250.

In some embodiments, the antimicrobial structure contains embeddedelectrodes in a configuration such that the antimicrobial agent iselectrically or electrochemically rechargeable. As intended herein,“rechargeable” refers to being chargeable during use as well as beinginitially chargeable when first deployed.

FIG. 3 is a sketch of an antimicrobial structure 305 (through-thicknessside view of coating or material) with a rechargeable antimicrobialagent. In FIG. 3, the antimicrobial structure 305 includes antimicrobialmaterial 300 a/300 b/300 c which is fabricated from the same componentsas the structure in FIG. 2, i.e., material 300 a/300 b/300 c includes asolid structural phase (210 in FIG. 2) and a continuous transport phase(220 in FIG. 2), which for purposes of clear illustration are shown inuniform grayscale in FIG. 3 as material 300 a/300 b/300 c.

In FIG. 3, there are two embedded electrodes 330 and 340 within theantimicrobial structure 305, wherein electrode 330 is depicted as apositive electrode layer and electrode 340 is depicted as a negativeelectrode layer. The electrode polarities may be switched. Theelectrodes may be fabricated from metal grids, meshes, or perforatedplates, for example, and may contain metals and catalysts such as Ti,Pt, Ru, Ir, or a combination thereof, for example. Electrode leads (notshown) will carry electrical current to or from the electrodes. Whilethe electrodes 330, 340 are depicted as embedded layers, other electrodeconfigurations are possible, including one or both electrodes beingouter layers, one of the electrodes being integrated with a basesubstrate or a wall of an object, or non-planar electrode architectures,for example.

In FIG. 3, there is an outer layer 350 that may contain microbes fromenvironmental sources (microbes not depicted) and is generally exposedto the environment. The structure 305 may be a coating on a substrate(not shown) or may be a bulk material or object, for example. Asubstrate, if present, would typically be distally opposite the outerlayer 350.

A suitable antimicrobial agent may be electrochemically charged orrecharged (e.g. after a period of use). In rechargeable configurations,the continuous transport phase will typically be wet with a liquidsolution containing water or another solvent, and/or a liquidelectrolyte (optionally, a gel electrolyte). The liquid solutioncontains an antimicrobial agent or a precursor to an antimicrobialagent. The liquid solution may contain a salt and/or a pH buffer aswell.

For example, when the selected antimicrobial agent is sodiumhypochlorite (NaClO) and/or hypochlorous acid (HOCl), sodium chloride(NaCl) may be used as an antimicrobial agent precursor. In particular,for example, a voltage may be applied such that NaCl dissolved in thetransport phase within material 300 b (between electrodes 330, 340) iselectrochemically transformed into sodium hypochlorite and/orhypochlorous acid, depending on the pH. NaClO and/or HOCl areantimicrobially active. After NaClO and/or HOCl are producedelectrochemically, the NaClO and/or HOCl permeates (via the continuoustransport phase) throughout the structure 305, i.e., from material 300 binto materials 300 a and 300 c. The desired location is material 300 a,especially near or at the outer layer 350, where microbes may beconcentrated. Since NaClO and/or HOCl present in material 300 c willtypically not be removed by environmental forces during use, there willnormally be a concentration gradient in the direction toward the outerlayer 350, which is desired for effective replenishment and thusrecharging. A periodic wash or soak with a salt solution (e.g.,2500-6000 ppm NaCl) and buffer may be used to maintain pH. A period soakwith a liquid electrolyte may be used to enhance transport rates of theantimicrobial agent or precursor thereof.

As another example, sodium hypochlorite and/or hypochlorous acid may begenerated by applying a voltage between electrodes 330, 340 as notedabove, wherein the NaClO and/or HOCl are antimicrobial agentprecursor(s) for recharging N-halamines that form the selectedantimicrobial agent.

The antimicrobial structure may further contain one or more protectivelayers, such as environmentally protective layer(s). Thus theantimicrobial structure may be a multilayer structure, which may containtwo layers, three layers, four layers, or more. In some embodiments,there is an outer layer to seal the active components from theenvironment while retaining and diffusing antimicrobial agents overtime.

There may be one or more capping layers that protect a liquid-like layerunderneath a capping layer, reducing evaporation of liquids. In theseembodiments, microbes (e.g., bacteria or viruses) may enter through acapping layer to reach the antimicrobial agent under the capping layer.Alternatively, or additionally, microbes may remain on the capping layerand antimicrobial agent diffuses through the capping layer to reach themicrobes.

In certain embodiments, the antimicrobial structure contains a poroustop layer and an absorbing inner layer that contains antimicrobialagents. In these embodiments, the porous top layer may include amaterial such as expanded polytetrafluoroethylene (e.g., Gore-Tex®),which allows vapor but not liquid to be exchanged. A bottom sealinglayer may be incorporated to prevent the loss of the antimicrobialagents.

In certain embodiments, the antimicrobial structure includes amulti-layer sub-structure wherein at least one layer contains thebiphasic architecture as disclosed herein, and wherein an internal orencapsulated layer contains antimicrobial agents and/or preferentiallytraps microbes to enhance antimicrobial effectiveness.

The antimicrobial structure may be characterized in that theantimicrobial agent has a diffusion coefficient (diffusivity) between10⁻¹⁶ m²/s and 10⁻⁹ m²/s, measured at a temperature of 25° C. and apressure of 1 bar, within the continuous transport phase. In variousembodiments, the antimicrobial agent diffusion coefficient is about, orat least about, 10⁻¹⁶ m²/s, preferably 10⁻¹⁴ m²/s, more preferably 10⁻¹²m²/s, even more preferably 10⁻¹⁰ m²/s, or most preferably 10⁻⁹ m²/s,measured at 25° C. and 1 bar. A diffusion coefficient on the order of10⁻⁹ m²/s is a liquid-like diffusion coefficient and is much higher,generally, than a purely solid-state diffusion coefficient.

The antimicrobial structure disclosed herein is not limited to transportof antimicrobial agent exclusively by pure diffusion. Depending on thespecific choice of materials, antimicrobial agent, and method of usingthe structure, the actual transport may occur by various mass-transfermechanisms including, but not limited to, Fickian diffusion, non-Fickiandiffusion permeation, sorption transport, solubility-diffusion,charge-driven flow, convection, capillary-driven flow, and so on. Asjust one example, when the antimicrobial structure is employed in anautomobile, the structure can move around quickly in space such that theantimicrobial agent undergoes some amount of centrifugal convection.

Even when the mass transport is dominated by diffusion, the actualtransport rate (flux) of antimicrobial agent through the structuredepends not only on the diffusion coefficient, but also on thethree-dimensional concentration gradient, temperature, and possiblyother factors such as pH. In various embodiments, the actual flux ofantimicrobial agent through the structure is about, or at least about,2×, 3×, 4×, 5×, 10×, 20×, 30×, 40×, 50×, 100×, 200×, 300×, 400×, 500×,or 1000× higher than the flux through a solid-state material. A personof ordinary skill in the art can calculate or estimate transport fluxesfor a given structure geometry and materials, or carry out experimentsto determine such fluxes.

The antimicrobial structure will be characterized by an originalconcentration of antimicrobial agent (prior to exposure to microbes).The original concentration of antimicrobial agent may be selected basedon the type of antimicrobial agent, and intended use of theantimicrobial structure, and/or other factors. In various embodiments,the original concentration of antimicrobial agent is about, at leastabout, or at most about 0.00001 wt %, 0.0001 wt %, 0.001 wt %, 0.01 wt%, 0.1 wt %, 1 wt %, 5 wt %, 10 wt %, 20 wt %, 30 wt %, 40 wt %, or 50wt %, on the basis of mass of antimicrobial agent divided by total massof all components within 0.1%, 1%, 5%, or 10% depth from the surfaceinto the bulk structure.

The antimicrobial structure may be characterized in that theantimicrobial agent is replenished on an outer surface of theantimicrobial structure to at least 25% of the original concentration ofantimicrobial agent, in 100 minutes or less. In various embodiments, theantimicrobial agent is replenished on an outer surface of theantimicrobial structure to at least 30%, 40%, 50%, 60%, 70%, 75%, 80%,85%, 90%, 95%, 99%, 99.9%, or 100% of the original concentration ofantimicrobial agent, in 100 minutes or less. In these or otherembodiments, the antimicrobial agent is replenished on an outer surfaceof the antimicrobial structure to at least 25% of the originalconcentration of antimicrobial agent, in 90, 80, 70, 60, 50, 40, 30, 20,15, 10, 5, 4, 3, 2, or 1 minutes or less. Preferably, the antimicrobialagent is replenished on an outer surface of the antimicrobial structureto at least 50% of the original concentration of antimicrobial agent, in60, 30, 20, 15, 10, 5, 4, 3, 2, or 1 minutes or less. These ranges maybe realized in embodiments without or with an electrically orelectrochemically rechargeable antimicrobial agent.

In some antimicrobial structures, the average phase-separation length isfrom about 0.5 microns to about 100 microns. In certain embodiments, theaverage phase-separation length is from about 1 micron to about 50microns. In various embodiments, the average phase-separation length isfrom 100 nanometers to 100 microns, 100 nanometers to 500 microns, 100nanometers to 100 microns, 100 nanometers to 200 microns, 100 nanometersto 200 microns, at least 200 nanometers, at least 500 nanometers, atleast 1 micron, at least 5 microns, up to 10 microns, up to 50 microns,up to 100 microns, or up to 500 microns. Exemplary averagephase-separation lengths are about, at least about, or at most about,0.1, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50, 60,70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 microns,including all intervening ranges.

The antimicrobial structure may be a coating or may be present in acoating. Alternatively, or additionally, the antimicrobial structure maybe present at a surface of a bulk object. The antimicrobial structuremay be the entirety of a bulk object, with no underlying substrate orother solid structure.

Various options may be incorporated into the antimicrobial structure, ora method of using the antimicrobial structure, to increase overallefficacy. For example, the antimicrobial structure may include physicalfeatures (e.g., nanorods or nanoporosity) that is of a similar lengthscale of viruses (e.g., about 50-150 nanometers) so that such physicalfeatures enhance the capture of viruses at the surface. The physicalfeatures may be fabricated from tethered quaternary ammonium compounds(see e.g., US 2019/0106525 which is incorporated by reference), alkylchains, or curable polycations (e.g., polyethyleneimine), for example.

An ionic layer may be combined with a triggered exothermic component toadd heat to the antimicrobial structure. For example, CaCl₂) may beincorporated as a solid additive in the antimicrobial structure to reactwith water (such as derived from an infected person's aerosol). The heatgenerated increases the rate of transport of antimicrobial agent. Forexample, see Chin et al., “Stability of SARS-CoV-2 in differentenvironmental conditions”, The Lancet Microbe, e10, Apr. 2, 2020(including supplemental content), which is incorporated by reference.

The continuous transport phase may be configured to solubilize virusesand/or bacteria to aid breaking up their outer surfaces. For example,detergent molecules may be included within the continuous transportphase. In certain embodiments, tethered alkyl chains or amphiphiles areadded to the continuous transport phase. Tethered alkyl chains oramphiphiles function similar to detergent molecules and will helpdisrupt bacteria or viral membranes. In these or other embodiments,surfactants may be included within the continuous transport phase.Surfactants may be anionic, cationic, zwitterionic, or non-ionicsurfactants.

The solid structural phase may be fabricated from, or include, ananti-fouling polymer to minimize the presence of dirt and debris (e.g.,oil) and to make the surface easier to clean. An exemplary anti-foulingpolymer is a segmented copolymer, further discussed below.

In some embodiments, an antimicrobial agent is incorporated into thecontinuous transport phase during synthesis of the antimicrobialstructure. In certain embodiments, an antimicrobial agent isincorporated into the continuous transport phase following synthesis ofthe antimicrobial structure, such as by infiltrating a liquid containingthe antimicrobial agent into the continuous transport phase, or byelectrochemically creating the antimicrobial agent in situ using avoltage applied between electrodes, for example.

Some embodiments will now be further described in reference to thesynthesis of the solid structural phase and the continuous transportphase, the preferred biphasic architecture, and the selectiveincorporation of an antimicrobial agent within the continuous transportphase.

Some embodiments are premised on the preferential incorporation of anantimicrobial agent within one phase of a multiphase polymer coating.The structure of a microphase-separated polymer network provides areservoir for antimicrobial agents within the continuous phase.

As intended herein, “microphase-separated” means that the first andsecond solid materials (e.g., soft segments) are physically separated ona microphase-separation length scale from about 0.1 microns to about 500microns.

Unless otherwise indicated, all references to “phases” in this patentapplication are in reference to solid phases or fluid phases. A “phase”is a region of space (forming a thermodynamic system), throughout whichall physical properties of a material are essentially uniform. Examplesof physical properties include density and chemical composition. A solidphase is a region of solid material that is chemically uniform andphysically distinct from other regions of solid material (or any liquidor vapor materials that may be present). Solid phases are typicallypolymeric and may melt or at least undergo a glass transition atelevated temperatures. Reference to multiple solid phases in acomposition or microstructure means that there are at least two distinctmaterial phases that are solid, without forming a solid solution orhomogeneous mixture.

In some embodiments, the antimicrobial agent is in a fluid. Preferably,the fluid is not solely in a vapor phase at 25° C., since vapor issusceptible to leaking from the structure. However, the fluid maycontain vapor in equilibrium with liquid, at 25° C. Also, in certainembodiments, a fluid is in liquid form at 25° C. but at least partiallyin vapor form at a higher use temperature, such as 30° C., 40° C., 50°C., or higher.

By a liquid being “disposed in” a solid material, it is meant that theliquid is incorporated into the bulk phase of the solid material, and/oronto surfaces of particles of the solid material. The liquid will be inclose physical proximity with the solid material, intimately and/oradjacently. The disposition is meant to include various mechanisms ofchemical or physical incorporation, including but not limited to,chemical or physical absorption, chemical or physical adsorption,chemical bonding, ion exchange, or reactive inclusion (which may convertat least some of the liquid into another component or a different phase,including potentially a solid). Also, a liquid disposed in a solidmaterial may or may not be in thermodynamic equilibrium with the localcomposition or the environment. Liquids may or may not be permanentlycontained in the structure; for example, depending on volatility orother factors, some liquid may be lost to the environment over time.

By “selectively” disposed in the continuous transport phase, or the“selectivity” into the continuous transport phase, it is meant that ofthe antimicrobial agent that is disposed within the structure overall,at least 51%, preferably at least 75%, and more preferably at least 90%of the antimicrobial agent is disposed in only the continuous transportphase. In various embodiments, the selectivity into the continuoustransport phase is about, or at least about, 60%, 65%, 70%, 75%, 80%,85%, 90%, 95%, 99%, or 100%.

In some embodiments, a liquid is added to a polymer such as bysubmerging and soaking into the polymer. In these embodiments, theliquid may be absorbed into a solid polymer. In certain embodiments, theliquid absorption swells a polymer, which means that there is anincrease of volume of polymer due to absorption of the liquid. Theliquid may be, but does not need to be, classified as a solvent for thesolid polymer which it swells.

The phase-separated microstructure preferably includes discrete islandsof one material (the solid structural phase) within a continuous sea ofthe other material (the continuous transport phase). The continuousphase provides unbroken channels within the material for transport ofmass and/or electrical charge.

In some embodiments, there are both phase-separated inclusions of thesame chemical material, as well as physically and chemically distinctmaterials as additional inclusions.

The solid structural phase and the continuous transport phase may bepresent as phase-separated regions of a copolymer, such as a blockcopolymer. As intended herein, a “block copolymer” means a copolymercontaining a linear arrangement of blocks, where each block is definedas a portion of a polymer molecule in which the monomeric units have atleast one constitutional or configurational feature absent from theadjacent portions. Segmented block copolymers are preferred, providingtwo (or more) phases. An exemplary segmented copolymer is aurethane-urea copolymer. In some embodiments, a segmented polyurethaneincludes a microphase-separated structure of fluorinated andnon-fluorinated species.

In some embodiments, a segmented copolymer is employed in which firstsoft segments form a continuous matrix and second soft segments are aplurality of discrete inclusions. In other embodiments, the first softsegments are a plurality of discrete inclusions and the second softsegments form a continuous matrix.

Segmented copolymers are typically created by combining a flexibleoligomeric soft segment terminated with an alcohol or amine reactivegroups and a multifunctional isocyanate. When the isocyanate is providedin excess relative to the alcohol/amine reactive groups, a viscousprepolymer mixture with a known chain length distribution is formed.This can then be cured to a high-molecular-weight network through theaddition of amine or alcohol reactive groups to bring the ratio ofisocyanate to amine/alcohol groups to unity. The product of thisreaction is a chain backbone with alternating segments: soft segments offlexible oligomers and hard segments of the reaction product oflow-molecular-weight isocyanates and alcohol/amines.

Due to the chemical immiscibility of these two phases, the materialtypically phase-separates on the length scale of these individualmolecular blocks, thereby creating a microstructure of flexible regionsadjacent to rigid segments strongly associated through hydrogen bondingof the urethane/urea moieties. This combination of flexible andassociated elements typically produces a physically crosslinkedelastomeric material.

Some variations of the invention utilize a segmented copolymercomposition comprising:

(a) one or more first soft segments selected from fluoropolymers havingan average molecular weight from about 500 g/mol to about 20,000 g/mol,wherein the fluoropolymers are (α,ω)-hydroxyl-terminated,(α,ω)-amine-terminated, and/or (α,ω)-thiol-terminated;

(b) one or more second soft segments selected from polyesters orpolyethers, wherein the polyesters or polyethers are(α,ω)-hydroxyl-terminated, (α,ω)-amine-terminated, and/or(α,ω)-thiol-terminated;

(c) one or more isocyanate species possessing an isocyanatefunctionality of 2 or greater, or a reacted form thereof;

(d) one or more polyol or polyamine chain extenders or crosslinkers, ora reacted form thereof,

wherein the first soft segments and the second soft segments may (insome embodiments) be microphase-separated on a microphase-separationlength scale from about 0.1 microns to about 500 microns, and

wherein optionally the molar ratio of the second soft segments to thefirst soft segments is less than 2.0.

In some embodiments, fluoropolymers are present in the triblockstructure:

wherein:X, Y═CH₂—(O—CH₂—CH₂)_(p)-T, and X and Y are independently selected;p=1 to 50;T is a hydroxyl, amine, or thiol terminal group;m=0 to 100 (in some embodiments, m=1 to 100); andn=0 to 100 (in some embodiments, n=1 to 100).

In some embodiments, the continuous transport phase includes apolyelectrolyte and a counterion to the polyelectrolyte. Thepolyelectrolyte may be selected from the group consisting ofpoly(acrylic acid) or copolymers thereof, cellulose-based polymers,carboxymethyl cellulose, chitosan, poly(styrene sulfonate) or copolymersthereof, poly(acrylic acid) or copolymers thereof, poly(methacrylicacid) or copolymers thereof, poly(allylamine), and combinations thereof,for example. The counterion may be selected from the group consisting ofH⁺, Li⁺, Na⁺, K⁺, Ag⁺, Ca²⁺, Mg²⁺, La³⁺, C₁₆N⁺, F⁻, Cl⁻, Br⁻, I⁻, BF₄ ⁻,SO₄ ²⁻, PO₄ ²⁻, C₁₂SO₃ ⁻, and combinations thereof, for example.

Other ionic species, combined with counterions, may be employed as wellin the continuous transport phase. Generally, in some embodiments, ionicspecies may be selected from the group consisting of an ionizable salt,an ionizable molecule, a zwitterionic component, a polyelectrolyte, anionomer, and combinations thereof.

An “ionomer” is a polymer composed of ionomer molecules. An “ionomermolecule” is a macromolecule in which a significant (e.g., greater than1, 2, 5, 10, 15, 20, or 25 mol %) proportion of the constitutional unitshave ionizable or ionic groups, or both.

The classification of a polymer as an ionomer versus polyelectrolytedepends on the level of substitution of ionic groups as well as how theionic groups are incorporated into the polymer structure. For example,polyelectrolytes also have ionic groups covalently bonded to the polymerbackbone, but have a higher ionic group molar substitution level (suchas greater than 50 mol %, usually greater than 80 mol %).Polyelectrolytes are polymers whose repeating units bear an electrolytegroup. Polyelectrolyte properties are thus similar to both electrolytes(salts) and polymers. Like salts, their solutions are electricallyconductive. Like polymers, their solutions are often viscous.

In some embodiments, the continuous transport phase includes a polymersuch as a polyurethane, a polyurea, a polysiloxane, or a combinationthereof, with at least some charge along the polymer backbone. Polymercharge may be achieved through the incorporation of ionic monomers suchas dimethylolpropionic acid, or another ionic species. The degree ofpolymer charge may vary, such as about, or at least about, 1, 2, 5, 10,15, 20, or 25 mol % of the polymer repeat units being ionic repeatunits.

In some embodiments, the continuous transport phase includes an ionicspecies selected from the group consisting of (2,2-bis-(1-(1-methylimidazolium)-methylpropane-1,3-diol bromide),1,2-bis(2′-hydroxyethyl)imidazolium bromide,(3-hydroxy-2-(hydroxymethyl)-2-methylpropyl)-3-methyl-1H-3λ⁴-imidazol-1-iumbromide, 2,2-bis(hydroxymethyl)butyric acid,N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid,N-methyl-2,2′-iminodiethanol, 3-dimethylamino-1,2-propanediol, 2,2-bis(hydroxymethyl)propionic acid, 1,4-bis(2-hydroxyethyl)piperazine,2,6-diaminocaproic acid, N,N-bis(2-hydroxyethyl)glycine,2-hydroxypropanoic acid hemicalcium salt, dimethylolpropionic acid,N-methyldiethanolamine, N-ethyldiethanolamine, N-propyldiethanolamine,N-benzyldiethanolamine, N-t-butyldiethanolamine, bis(2-hydroxyethyl)benzylamine, bis(2-hydroxypropyl) aniline, and homologues, combinations,derivatives, or reaction products thereof.

A liquid may be introduced into the continuous transport phase actively,passively, or a combination thereof. In some embodiments, a liquid isactively introduced to the continuous transport phase by spraying of theliquid, deposition from a vapor phase derived from the liquid, liquidinjection, bath immersion, or other techniques. In some embodiments, aliquid is passively introduced to the continuous transport phase byletting the liquid naturally be extracted from the normal atmosphere, orfrom a local atmosphere adjusted to contain one or more desired liquidsin vapor or droplet (e.g., mist) form.

In certain embodiments, a desired additive is normally a solid at roomtemperature and is first dissolved or suspended in a liquid that is thendisposed in the continuous transport phase.

In other certain embodiments, a desired additive is normally a solid atroom temperature and is first melted to produce a liquid that is thendisposed in the continuous transport phase. Within the continuoustransport phase, the desired additive may partially or completelysolidify back to a solid, or may form a multiphase material, forexample.

Some potential additives contain reactive groups that unintentionallyreact with chemical groups contained in the polymer precursors.Therefore, in some cases, there exists an incompatibility of liquidspecies in the resin during chemical synthesis and polymerization.Addition of reactive fluid additives into the reaction mixture duringsynthesis can dramatically alter stoichiometry and backbone structure,while modifying physical and mechanical properties. One strategy tocircumvent this problem is to block the reactive groups (e.g., alcohols,amines, and/or thiols) in the fluid additive with chemical protectinggroups to render them inert to reaction with other reactive chemicalgroups (e.g., isocyanates) in the coating precursors.

In particular, it is possible to temporarily block a reactive positionby transforming it into a new functional group that will not interferewith the desired transformation. That blocking group is conventionallycalled a “protecting group.” Incorporating a protecting group into asynthesis requires at least two chemical reactions. The first reactiontransforms the interfering functional group into a different one thatwill not compete with (or compete at a lower reaction rate with) thedesired reaction. This step is called protection. The second chemicalstep transforms the protecting group back into the original group at alater stage of synthesis. This latter step is called deprotection.

In some embodiments in which an additive contains alcohol, amine, and/orthiol groups, the additive thus contains chemical protecting groups toprevent or inhibit reaction of the alcohol, amine, and/or thiol groupswith isocyanates. The protecting groups may be designed to undergodeprotection upon reaction with atmospheric moisture, for example.

In the case of an additive containing alcohol groups, the protectinggroups may be selected from the silyl ether class of alcohol protectinggroups. For example, the protecting groups may be selected from thegroup consisting of trimethylsilyl ether, isopropyldimethylsilyl ether,tert-butyldimethylsilyl ether, tert-butyldiphenylsilyl ether,tribenzylsilyl ether, triisopropylsilyl ether, and combinations thereof.In these or other embodiments, the protecting groups to protect alcoholmay be selected from the group consisting of 2,2,2-trichloroethylcarbonate, 2-methoxyethoxymethyl ether, 2-naphthylmethyl ether,4-methoxybenzyl ether, acetate, benzoate, benzyl ether, benzyloxymethylacetal, ethoxyethyl acetal, methoxymethyl acetal, methoxypropyl acetal,methyl ether, tetrahydropyranyl acetal, triethylsilyl ether, andcombinations thereof.

In the case of an additive containing amine groups, the protectinggroups may be selected from the carbamate class of amine protectinggroups, such as (but not limited to) vinyl carbamate. Alternatively, oradditionally, the protecting groups may be selected from the ketamineclass of amine protecting groups. In these or other embodiments, theprotecting groups to protect amine may be selected from the groupconsisting of 1-chloroethyl carbamate, 4-methoxybenzenesulfonamide,acetamide, benzylamine, benzyloxy carbamate, formamide, methylcarbamate, trifluoroacetamide, tert-butoxy carbamate, and combinationsthereof.

In the case of an additive containing thiol groups, the protectinggroups may be selected from S-2,4-dinitrophenyl thioether and/orS-2-nitro-1-phenylethyl thioether, for example.

The typical reaction mechanism when water is the deprotecting reagent issimple hydrolysis. Water is often nucleophilic enough to kick off aleaving group and deprotect a species. One example of this is theprotection of an amine with a ketone to form a ketamine. These can bemixed with isocyanates when the amine alone would react so quickly as tonot be able to be practically mixed. Instead the ketamine reagent isinert but after mixing and casting as a film, atmospheric moisture willdiffuse into the coating, remove the ketone (which vaporizes itself) andleaves the amine to rapidly react with neighboring isocyanates in situ.

Many deprotecting agents require high pH, low pH, or redox chemistry towork. However, some protecting groups are labile enough that water aloneis sufficient to cause deprotection. When possible, a preferred strategyto spontaneously deprotect the molecules is through reaction withatmospheric moisture, such as an atmosphere containing from about 10% toabout 90% relative humidity at ambient temperature and pressure. Awell-known example is the room-temperature vulcanization of silicones.These systems have silyl ethers that are deprotected with moisture andin doing so the free Si—OH reacts with other silyl ethers to createSi—O—Si covalent bonds, forming a network.

In other embodiments, a chemical deprotection step is activelyconducted, such as by introducing a deprotection agent and/or adjustingmixture conditions such as temperature, pressure, pH, solvents,electromagnetic field, or other parameters.

This specification hereby incorporates by reference herein Greene andWuts, Protective Groups in Organic Synthesis, Fourth Edition, John Wiley& Sons, New York, 2007, for its teachings of the role of protectinggroups, synthesis of protecting groups, and deprotection schemesincluding for example adjustment of pH by addition of acids or bases, tocause deprotection.

As intended in this patent application, “hygroscopic” means that amaterial is capable of attracting and holding water molecules from thesurrounding environment. The water uptake of various polymers isdescribed in Thijs et al., “Water uptake of hydrophilic polymersdetermined by a thermal gravimetric analyzer with a controlled humiditychamber” J. Mater. Chem., (17) 2007, 4864-4871, which is herebyincorporated by reference herein. In some embodiments, a hygroscopicmaterial is characterized by a water absorption capacity, at 90%relative humidity and 30° C., of at least 5, 10, 15, 20, 25, 30, 35, 40,45, or 50 wt % uptake of H₂O.

In some embodiments employing segmented copolymers, one of the firstsoft segments and second soft segments is oleophobic. An oleophobicmaterial has a poor affinity for oils. As intended herein, the term“oleophobic” means a material with a contact angle of hexadecane greaterthan 90°. An oleophobic material may also be classified as lipophobic.

In some embodiments employing segmented copolymers, one of the firstsoft segments and the second soft segments may be a “low-surface-energypolymer” which means a polymer, or a polymer-containing material, with asurface energy of no greater than 50 mJ/m². In some embodiments, one ofthe first soft segments and the second soft segments has a surfaceenergy from about 5 mJ/m² to about 50 mJ/m².

In some embodiments employing segmented copolymers, the first softsegments or the second soft segments may be or include a fluoropolymer,such as (but not limited to) a fluoropolymer selected from the groupconsisting of polyfluoroethers, perfluoropolyethers, fluoroacrylates,fluorosilicones, polytetrafluoroethylene (PTFE), polyvinylidenedifluoride (PVDF), polyvinylfluoride (PVF), polychlorotrifluoroethylene(PCTFE), copolymers of ethylene and trifluoroethylene, copolymers ofethylene and chlorotrifluoroethylene, and combinations thereof.

In these or other embodiments, the first soft segments or the secondsoft segments may be or include a siloxane. A siloxane contains at leastone Si—O—Si linkage. The siloxane may consist of polymerized siloxanesor polysiloxanes (also known as silicones). One example ispolydimethylsiloxane.

In some embodiments, the molar ratio of the second soft segments to thefirst soft segments is about 2.0 or less. In various embodiments, themolar ratio of the second soft segments to the first soft segments isabout 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2,1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 1.95.

It is noted that (α,ω)-terminated polymers are terminated at each end ofthe polymer. The α-termination may be the same or different than theco-termination on the opposite end. The fluoropolymers and/or thepolyesters or polyethers may terminated with a combination of hydroxylgroups, amine groups, and thiol groups, among other possible terminationgroups. Note that thiols can react with an —NCO group (usually catalyzedby tertiary amines) to generate a thiourethane.

Also it is noted that in this disclosure, “(α,ω)-termination” includesbranching at the ends, so that the number of terminations may be greaterthan 2 per polymer molecule. The polymers herein may be linear orbranched, and there may be various terminations and functional groupswithin the polymer chain, besides the end (α,ω) terminations.

In this description, “polyurethane” is a polymer comprising a chain oforganic units joined by carbamate (urethane) links, where “urethane”refers to N(H)—(C═O)—O—. Polyurethanes are generally produced byreacting an isocyanate containing two or more isocyanate groups permolecule with one or more polyols containing on average two or morehydroxyl groups per molecule, in the presence of a catalyst.

Polyols are polymers with on average two or more hydroxyl groups permolecule. For example, α,ω-hydroxyl-terminated perfluoropolyether is atype of polyol.

“Isocyanate” is the functional group with the formula —N═C═O. For thepurposes of this disclosure, O—C(═O)—N(H)—R is considered a derivativeof isocyanate. “Isocyanate functionality” refers to the number ofisocyanate reactive sites on a molecule. For example, diisocyanates havetwo isocyanate reactive sites and therefore an isocyanate functionalityof 2. Triisocyanates have three isocyanate reactive sites and thereforean isocyanate functionality of 3.

“Polyfluoroether” refers to a class of polymers that contain an ethergroup—an oxygen atom connected to two alkyl or aryl groups, where atleast one hydrogen atom is replaced by a fluorine atom in an alkyl oraryl group.

“Perfluoropolyether” (PFPE) is a highly fluorinated subset ofpolyfluoroethers, wherein all hydrogen atoms are replaced by fluorineatoms in the alkyl or aryl groups.

“Polyurea” is a polymer comprising a chain of organic units joined byurea links, where “urea” refers to N(H)—(C═O)—N(H)—. Polyureas aregenerally produced by reacting an isocyanate containing two or moreisocyanate groups per molecule with one or more multifunctional amines(e.g., diamines) containing on average two or more amine groups permolecule, optionally in the presence of a catalyst.

A “chain extender or crosslinker” is a compound (or mixture ofcompounds) that link long molecules together and thereby complete apolymer reaction. Chain extenders or crosslinkers are also known ascuring agents, curatives, or hardeners. In polyurethane/urea systems, acurative is typically comprised of hydroxyl-terminated oramine-terminated compounds which react with isocyanate groups present inthe mixture. Diols as curatives form urethane linkages, while diaminesas curatives form urea linkages. The choice of chain extender orcrosslinker may be determined by end groups present on a givenprepolymer. In the case of isocyanate end groups, curing can beaccomplished through chain extension using multifunctional amines oralcohols, for example. Chain extenders or crosslinkers can have anaverage functionality greater than 2 (such as 2.5, 3.0, or greater),i.e. beyond diols or diamines.

In some embodiments, polyesters or polyethers are selected from thegroup consisting of poly(oxymethylene), poly(ethylene glycol),poly(propylene glycol), poly(tetrahydrofuran), poly(glycolic acid),poly(caprolactone), poly(ethylene adipate), poly(hydroxybutyrate),poly(hydroxyalkanoate), and combinations thereof.

In some embodiments, the isocyanate species is selected from the groupconsisting of 4,4′-methylenebis(cyclohexyl isocyanate), hexamethylenediisocyanate, cycloalkyl-based diisocyanates, tolylene-2,4-diisocyanate,4,4′-methylenebis(phenyl isocyanate), isophorone diisocyanate, andcombinations or derivatives thereof.

The polyol or polyamine chain extender or crosslinker possesses afunctionality of 2 or greater, in some embodiments. At least one polyolor polyamine chain extender or crosslinker may be selected from thegroup consisting of 1,4-butanediol, 1,3-propanediol, 1,2-ethanediol,glycerol, trimethylolpropane, ethylenediamine, isophoronediamine,diaminocyclohexane, and homologues, derivatives, or combinationsthereof. In some embodiments, polymeric forms of polyol chain extendersor crosslinkers are utilized, typically hydrocarbon or acrylic backboneswith hydroxyl groups distributed along the side groups.

The one or more chain extenders or crosslinkers (or reaction productsthereof) may be present in a concentration, in the segmented copolymercomposition, from about 0.01 wt % to about 25 wt %, such as from about0.05 wt % to about 10 wt %.

First soft segments may be present in a concentration from about 5 wt %to about 95 wt % based on total weight of the composition. In variousembodiments, the first soft segments may be present in a concentrationof about 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 95 wt % based ontotal weight of the composition. Second soft segments may be present ina concentration from about 5 wt % to about 95 wt % based on total weightof the composition. In various embodiments, the second soft segments maybe present in a concentration of about 5, 10, 20, 30, 40, 50, 60, 70,80, 90, or 95 wt % based on total weight of the composition.

In some embodiments, fluorinated polyurethane oligomers are terminatedwith silane groups. The end groups on the oligomers (in the prepolymer)may be modified from isocyanate to silyl ethers. This can beaccomplished through reaction of an isocyanate-reactive silane species(e.g., aminopropyltriethoxysilane) to provide hydrolysable groupswell-known in silicon and siloxane chemistry. Such an approacheliminates the need for addition of a stoichiometric amount of curativeto form strongly associative hard segments, while replacing the curativewith species that possess the ability to form a covalently crosslinkednetwork under the influence of moisture or heat. Such chemistry has beenshown to preserve beneficial aspects of urethane coatings while boostingscratch resistance.

In addition, the reactivity of the terminal silane groups allows foradditional functionality in the form of complimentary silanes blendedwith the prepolymer mixture. The silanes are able to condense into thehydrolysable network upon curing. This strategy allows for discretedomains of distinct composition. A specific embodiment relevant toanti-fouling involves the combination of fluoro-containing urethaneprepolymer that is endcapped by silane reactive groups with additionalalkyl silanes.

In some embodiments employing segmented copolymers, themicrophase-separated microstructure containing the first and second softsegments may be characterized as an inhomogeneous microstructure. Asintended in this patent application, “phase inhomogeneity,”“inhomogeneous microstructure,” and the like mean that a multiphasemicrostructure is present in which there are at least two discretephases that are separated from each other. The two phases may be onediscrete solid phase in a continuous solid phase, two co-continuoussolid phases, or two discrete solid phases in a third continuous solidphase, for example. The length scale of phase inhomogeneity may refer tothe average size (e.g., effective diameter) of discrete inclusions ofone phase dispersed in a continuous phase. The length scale of phaseinhomogeneity may refer to the average center-to-center distance betweennearest-neighbor inclusions of the same phase. The length scale of phaseinhomogeneity may alternatively refer to the average separation distancebetween nearest-neighbor regions of the discrete (e.g., droplets) phase,where the distance traverses the continuous phase.

The average length scale of phase inhomogeneity may generally be fromabout 0.1 microns to about 500 microns. In some embodiments, the averagelength scale of phase inhomogeneity is from about 0.5 microns to about100 microns, such as about 1 micron to about 50 microns. In variousembodiments, the average length scale of phase inhomogeneity is about0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 10, 15, 20,25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350,400, 450, or 500 microns, including any intermediate values notexplicitly recited, and ranges starting, ending, or encompassing suchintermediate values. These are average values, noting that a portion ofphase inhomogeneity may be present on a length scale less than 0.1micron or greater than 500 microns (e.g., about 1000 microns), with theoverall average falling in the range of 0.1-500 microns. Note that inthis disclosure, “about 0.1 microns” is intended to encompass 0.05-0.149microns (50-149 nanometers), i.e. ordinary rounding.

This phase inhomogeneity typically causes opaque coatings or films dueto the scattering of light. Scattering of light including visiblewavelengths in the bulk of a material is governed by changes in theindex of refraction through the medium. Variations in refractive indexat length scales near the wavelength of the propagating radiation willtend to scatter those wavelengths more effectively (Mie scattering),resulting in an opaque or white appearance for a coating. With visiblelight having a wavelength range of about 400-700 nm, a clear ortransparent coating must typically keep variations in index ofrefraction below about 50 nm in length. As phase inhomogeneitiesincrease in length scale, the opacity of the material rises. Phaseinhomogeneities with average length scale from 0.1 μm to 500 μm areexpected to drive significant scattering in the material, leading toopaque structures above 25 μm in thickness—unless the multiple phaseshappen to be refractive index-matched. See Althues et al., “Functionalinorganic nanofillers for transparent polymers” Chem. Soc. Rev., 2007,36, 1454-1465, which is hereby incorporated by reference herein for itsteaching that materials with inhomogeneity below 50 nm will tend to beclear, and materials with inhomogeneity above 50 nm (0.05 μm) will tendto be opaque.

In some embodiments, the antimicrobial structure is opaque with respectto ordinary light. In some embodiments, the antimicrobial structure issemi-transparent or transparent with respect to ordinary light. Incertain embodiments, different phases of the antimicrobial structure areselected such that the respective refraction indices are matched orsubstantially similar. One example is polytetrahydrofuran withpoly(ethylene glycol), which are index-matched to within about 1%.Another example is polytetrahydrofuran with poly(propylene glycol),which are index-matched to within 2%. In some embodiments, the solidtransport material and the solid structural material are selected suchthat the index of refraction of the solid structural material is within±10%, preferably within ±5%, more preferably with ±2%, and mostpreferably with ±1%.

The antimicrobial structure may also be characterized by hierarchicalphase separation. For example, when segmented copolymers are utilized,first soft segments and second soft segments—in addition to beingmicrophase-separated—are typically nanophase-separated. As intendedherein, two materials being “nanophase-separated” means that the twomaterials are separated from each other on a length scale from about 1nanometer to about 100 nanometers. For example, the nanophase-separationlength scale may be from about 10 nanometers to about 100 nanometers.

The nanophase separation between first solid material (or phase) andsecond solid material (or phase) may be caused by the presence of athird solid material (or phase) disposed between regions of the firstand second solid materials. For example, in the case of first and secondsolid materials being soft segments of a segmented copolymer also withhard segments, the nanophase separation may be driven by intermolecularassociation of hydrogen-bonded, dense hard segments. In these cases, insome embodiments, the first soft segments and the hard segments arenanophase-separated on an average nanophase-separation length scale fromabout 10 nanometers to less than 100 nanometers. Alternatively, oradditionally, the second soft segments and the hard segments may benanophase-separated on an average nanophase-separation length scale fromabout 10 nanometers to less than 100 nanometers. The first and secondsoft segments themselves may also be nanophase-separated on an averagenanophase-separation length scale from about 10 nanometers to less than100 nanometers, i.e., the length scale of the individual polymermolecules.

The nanophase-separation length scale is hierarchically distinct fromthe microphase-separation length scale. With traditional phaseseparation in block copolymers, the blocks chemically segregate at themolecular level, resulting in regions of segregation on the length scaleof the molecules, such as a nanophase-separation length scale from about10 nanometers to about 100 nanometers. Again see Petrovic et al.,“POLYURETHANE ELASTOMERS” Prog. Polym. Sci., Vol. 16, 695-836, 1991. Theextreme difference of the two soft segments means that in the reactionpot the soft segments do not mix homogeneously and so create discreteregion that are rich in fluoropolymer or rich in non-fluoropolymer(e.g., PEG) components, distinct from the molecular-level segregation.These emulsion droplets contain a large amount of polymer chains and arethus in the micron length-scale range. These length scales survive thecuring process, so that the final material contains the microphaseseparation that was set-up from the emulsion, in addition to themolecular-level (nanoscale) segregation.

In some embodiments, therefore, the larger length scale of separation(0.1-500 microns) is driven by an emulsion process, which providesmicrophase separation that is in addition to classic molecular-levelphase separation. Chen et al., “Structure and morphology of segmentedpolyurethanes: 2. Influence of reactant incompatibility” POLYMER, 1983,Vol. 24, pages 1333-1340, is hereby incorporated by reference herein forits teachings about microphase separation that can arise from anemulsion-based procedure.

In some embodiments, discrete inclusions have an average size (e.g.,effective diameter) from about 50 nm to about 150 μm, such as from about100 nm to about 100 μm. In various embodiments, discrete inclusions havean average size (e.g., effective diameter) of about 50 nm, 100 nm, 200nm, 500 nm, 1 μm, 2 μm, 5 μm, 10 μm, 50 μm, 100 pm, or 200 μm.

In these or other embodiments, discrete inclusions (of solid structuralphase) have an average center-to-center spacing between adjacentinclusions, through a continuous matrix (of continuous transport phase),from about 50 nm to about 150 μm, such as from about 100 nm to about 100μm. In various embodiments, discrete inclusions have an averagecenter-to-center spacing between adjacent inclusions of about 50 nm, 100nm, 200 nm, 500 nm, 1 μm, 2 μm, 5 μm, 10 μm, 50 μm, 100 μm, or 200 μm.

In some variations of the invention, the antimicrobial structure forms acoating disposed on a substrate. The coating may have a thickness fromabout 1 μm to about 10 mm, for example. In various embodiments, thecoating thickness is about 100 nm, 1 μm, 10 μm, 100 μm, 1 mm, or 10 mm.Thicker coatings provide the benefit that even after surface abrasion,the coating still functions because the entire depth of the coating (notjust the outer surface) contains the functional materials. The coatingthickness will generally depend on the specific application.

An optional substrate may be disposed on the back side of theantimicrobial structure. A substrate will be present when the materialforms a coating or a portion of a coating (e.g., one layer of amultilayer coating). Many substrates are possible, such as a metal,polymer, wood, or glass substrate. Essentially, the substrate may be anymaterial or object for which antimicrobial protection is desirable.

In some embodiments, an adhesion layer is disposed on a substrate,wherein the adhesion layer is configured to promote adhesion of theantimicrobial structure to the selected substrate. An adhesion layercontains one or more adhesion-promoting materials, such as (but notlimited to) primers (e.g., carboxylated styrene-butadiene polymers),alkoxysilanes, zirconates, and titanium alkoxides.

Various strategies are possible to form the materials of theantimicrobial structure, as will be appreciated by a skilled artisan.

In some embodiments, the antimicrobial structure is in the form of anapplique that may be adhered to a surface at the point of use.

Prior to formation of the final antimicrobial structure, a precursorcomposition may be provided. The precursor composition may bewaterborne, solventborne, or a combination thereof. In some waterborneembodiments, first or second soft segments may be derived from anaqueous dispersion of a linear crosslinkable polyurethane containingcharged groups, and the other soft segments may be derived from acrosslinking agent containing charged groups, for example.

In some embodiments, a precursor includes a silane, a silyl ether, asilanol, an alcohol, or a combination or reaction product thereof, andoptionally further includes a protecting group that protects theprecursor from reacting with other components.

Some embodiments employ waterborne polyurethane dispersions. Asuccessful waterborne polyurethane dispersion sometimes requires thespecific components to contain ionic groups to aid in stabilizing theemulsion. Other factors contributing to the formulation of a stabledispersion include the concentration of ionic groups, concentration ofwater or solvent, and rate of water addition and mixing during theinversion process. An isocyanate prepolymer may be dispersed in water.Subsequently, a curative component may be dispersed in water. Waterevaporation then promotes the formation of a microphase-separatedpolyurethane material.

A composition or precursor composition may generally be formed from aprecursor material (or combination of materials) that may be provided,obtained, or fabricated from starting components. The precursor materialis capable of hardening or curing in some fashion, to form a precursorcomposition containing the first soft segments and second soft segments,microphase-separated on a microphase-separation length scale from about0.1 microns to about 500 microns. The precursor material may be aliquid; a multiphase liquid; a multiphase slurry, emulsion, orsuspension; a gel; or a dissolved solid (in solvent), for example.

In some embodiments, an emulsion sets up in the reaction mixture basedon incompatibility between the two blocks (e.g., PEG and PFPE). Theemulsion provides microphase separation in the precursor material. Theprecursor material is then cured from casting or spraying. Themicrophase separation survives the curing process (even if the lengthscales change somewhat during curing), providing the benefits in thefinal materials (or precursor compositions) as described herein. Withoutbeing limited by theory, the microphase separation in this invention isnot associated with molecular length-scale separation (5-50 nm) thatmany classic block-copolymer systems exhibit. Rather, the larger lengthscales of microphase separation, i.e. 0.1-500 μm, arise from theemulsion that was set-up prior to curing.

Xu et al., “Structure and morphology of segmented polyurethanes: 1.Influence of incompatibility on hard-segment sequence length” POLYMER,1983, Vol. 24, pages 1327-1332 and Chen et al., “Structure andmorphology of segmented polyurethanes: 2. Influence of reactantincompatibility” POLYMER, 1983, Vol. 24, pages 1333-1340, are eachhereby incorporated by reference herein for their teachings aboutemulsion set-up in polyurethane systems prior to curing.

In some variations of the invention, a precursor material is applied toa substrate and allowed to react, cure, or harden to form a finalcomposition (e.g., coating). In some embodiments, a precursor materialis prepared and then dispensed (deposited) over an area of interest. Anyknown methods to deposit precursor materials may be employed. A fluidprecursor material allows for convenient dispensing using spray coatingor casting techniques.

The fluid precursor material may be applied to a surface using anycoating technique, such as (but not limited to) spray coating, dipcoating, doctor-blade coating, air knife coating, curtain coating,single and multilayer slide coating, gap coating, knife-over-rollcoating, metering rod (Meyer bar) coating, reverse roll coating, rotaryscreen coating, extrusion coating, casting, or printing. Becauserelatively simple coating processes may be employed, rather thanlithography or vacuum-based techniques, the fluid precursor material maybe rapidly sprayed or cast in thin layers over large areas (such asmultiple square meters).

When a solvent or carrier fluid is present in a fluid precursormaterial, the solvent or carrier fluid may include one or more compoundsselected from the group consisting of water, alcohols (such as methanol,ethanol, isopropanol, or tert-butanol), ketones (such as acetone, methylethyl ketone, or methyl isobutyl ketone), hydrocarbons (e.g., toluene),acetates (such as tert-butyl acetate), acids (such as organic acids),bases, and any mixtures thereof. When a solvent or carrier fluid ispresent, it may be in a concentration of from about 10 wt % to about 99wt % or higher, for example.

The precursor material may be converted to an intermediate material orthe final composition using any one or more of curing or other chemicalreactions, or separations such as removal of solvent or carrier fluid,monomer, water, or vapor. Curing refers to toughening or hardening of apolymeric material by physical crosslinking, covalent crosslinking,and/or covalent bonding of polymer chains, assisted by electromagneticwaves, electron beams, heat, and/or chemical additives. Chemical removalmay be accomplished by heating/flashing, vacuum extraction, solventextraction, centrifugation, etc. Physical transformations may also beinvolved to transfer precursor material into a mold, for example.Additives may be introduced during the hardening process, if desired, toadjust pH, stability, density, viscosity, color, or other properties,for functional, ornamental, safety, or other reasons.

EXAMPLES Example 1: Synthesis of Polymeric Antimicrobial Structure

Polyethylene glycol (M_(n)=400 g/mol, 9.88 g), fluoropolymer FluorolinkE10H (M_(n)=1800 g/mol, 10.0 g), polyisocyanate Desmodur 3300(equivalent weight=193, 9.54 g) and dibutyltin dilaurate (2000 ppm) arecombined in a polypropylene cup. Ratios of polyethylene glycol andfluoropolymer are adjusted to produce a 60 vol %/40 vol % ratio,respectively. This mixture is then and placed in a centrifugal mixer (2min, 2000 rpm) and homogenized. The resin is then cast onbiaxially-oriented polyethylene terephthalate (Mylar) with a releasefilm using a doctor blade and left to cure at room temperature.

Example 2: Synthesis of Polymeric Antimicrobial Structure

Poly(tetramethylene glycol) (M_(n)=650 g/mol, 10.00 g) (also known aspolyTHF or pTHF), polyethylene glycol (M_(n)=600 g/mol, 3.81 g) (alsoknown as PEG), polyisocyanate Desmodur 3300 (equivalent weight=193, 8.39g) and dibutyltin dilaurate (2000 ppm) are combined in a polypropylenecup. Ratios of poly(tetramethylene glycol) and polyethylene glycol areadjusted to produce a 75 vol %/25 vol % ratio, respectively. Thismixture is then placed in a centrifugal mixer (2 min, 2000 rpm) andhomogenized. The resin is then cast on Mylar with a release film using adoctor blade and left to cure at room temperature.

Example 3: Electrochemical Impedance Spectroscopy (EIS) of AntimicrobialAgent Transport in Polymer Films

The transport rate of a selected antimicrobial agent (10% benzalkoniumchloride in water) is measured in a series of PEG-polyTHF films usingelectrochemical impedance spectroscopy (EIS). The typical film surfacearea is 1.08 cm² with a thickness of about 0.02 cm. Measurements areperformed in a two-electrode electrochemical cell at frequencies between10² and 5×10⁶ Hz.

FIG. 4 shows the magnitude of the impedance spectra (normalized by thefilm thickness) for six films with various PEG concentrations (0 vol %,25 vol %, 40 vol %, 50 vol %, 60 vol %, and 75 vol % PEG, with theremainder pTHF) after immersion in a 10% benzalkonium chloride (inwater) solution for approximately 2 days. As a comparison, thenormalized impedance spectra for a pure solution of 10% benzalkoniumchloride in water is also shown. In FIG. 4, “quat” refers to 10%benzalkonium chloride. Specific conductivity and diffusion coefficientsare measured from the impedance at 10⁴ Hz (dashed vertical line in FIG.4).

FIG. 5 shows a plot of the specific conductivity (left axis) anddiffusion coefficients (right axis) as a function of PEG concentration(0 vol %, 25 vol %, 40 vol %, 50 vol %, 60 vol %, and 75 vol %) afterimmersion in a 10% benzalkonium chloride (in water) solution forapproximately 2 days. Conductivity and diffusion coefficients aredetermined from the impedance at 10 kHz. The dashed near at the top ofFIG. 5 represents the conductivity and diffusion coefficient of a puresolution of 10% benzalkonium chloride in water.

The specific conductivity of the benzalkonium chloride in the film with25 vol % PEG is about 400× greater than that of the pure pTHF film. Thismeasurement suggests a small amount of a transport phase (e.g., PEG) issufficient to achieve rapid transport of benzalkonium chloride in thesefilms. The transport rate of the benzalkonium chloride (theconductivity) increase with PEG concentration, increasing an additional30× at 75 vol % PEG.

Example 4: Use of Antimicrobial Structure

This example illustrates one antimicrobial structure and one commercialmethod of using the antimicrobial structure. The structure and method ofusing it are not intended to limit the scope of the invention in anyway.

An antimicrobial structure is fabricated with a discrete solidstructural phase of perfluoropolyethers, a continuous transport phase ofpoly(ethylene oxide) and optionally polyacrylic acid and/or2-phenoxyethanol electrolytes, a trifunctional isocyanate ascrosslinking agent to lock in the network structure, and quaternaryammonium biocides as the antimicrobial agent.

A shared vehicle such as a taxi incorporates a disclosed antimicrobialstructure as a seat coating. A first occupant enters the vehicle and, inthe process of entering, removes a portion of the antimicrobial agent atthat surface. Less than an hour later, a second occupant coughs anddeposits an amount of active virus onto the seat surface. The seatsurface was quickly and automatically replenished of antimicrobial agent(quaternary ammonium biocides) according to the principles set forth inthis disclosure, due to fast transport from the continuous transportphase. The antimicrobial agent inactivates the virus from the secondoccupant. Less than an hour later, a third occupant enters the sameshared vehicle and touches the same surface, but the third occupant doesnot become infected since the viral load at the seat surface has beenreduced to very low levels that are no longer infectious to humans.

In this detailed description, reference has been made to multipleembodiments and to the accompanying drawings in which are shown by wayof illustration specific exemplary embodiments of the invention. Theseembodiments are described in sufficient detail to enable those skilledin the art to practice the invention, and it is to be understood thatmodifications to the various disclosed embodiments may be made by askilled artisan.

Where methods and steps described above indicate certain eventsoccurring in certain order, those of ordinary skill in the art willrecognize that the ordering of certain steps may be modified and thatsuch modifications are in accordance with the variations of theinvention. Additionally, certain steps may be performed concurrently ina parallel process when possible, as well as performed sequentially.

All publications, patents, and patent applications cited in thisspecification are herein incorporated by reference in their entirety asif each publication, patent, or patent application were specifically andindividually put forth herein.

The embodiments, variations, and figures described above should providean indication of the utility and versatility of the present invention.Other embodiments that do not provide all of the features and advantagesset forth herein may also be utilized, without departing from the spiritand scope of the present invention. Such modifications and variationsare considered to be within the scope of the invention defined by theclaims.

1. An antimicrobial structure comprising: (a) a solid structural phase comprising a solid structural material; (b) a continuous transport phase that is interspersed within said solid structural phase, wherein said continuous transport phase comprises a gel electrolyte, wherein said gel electrolyte contains (i) an electrolyte salt, (ii) an aqueous or non-aqueous solvent, and (iii) a polymer host comprising a solid transport material; and (c) an antimicrobial agent contained within said continuous transport phase, wherein said solid structural phase and said continuous transport phase are separated by an average phase-separation length from about 100 nanometers to about 500 microns.
 2. The antimicrobial structure of claim 1, wherein said solid structural material is a solid structural polymer selected from the group consisting of a non-fluorinated carbon-based polymer, a silicone, a fluorinated polymer, and combinations thereof.
 3. The antimicrobial structure of claim 2, wherein said non-fluorinated carbon-based polymers are selected from the group consisting of polyalkanes, polyurethanes, polyethers, polyureas, polyesters, and combinations thereof.
 4. The antimicrobial structure of claim 2, wherein said silicones are selected from the group consisting of polydimethyl siloxane, polytrifluoropropylmethyl siloxane, polyaminopropylmethyl siloxane, polyaminoethylaminopropylmethyl siloxane, polyaminoethylaminoisobutylmethyl siloxane, and combinations thereof.
 5. The antimicrobial structure of claim 2, wherein said fluorinated polymers are selected from the group consisting of fluorinated polyols, perfluorocarbons, perfluoropolyethers, polyfluoroacrylates, polyfluorosiloxanes, polyvinylidene fluoride, polytrifluoroethylene, and combinations thereof.
 6. The antimicrobial structure of claim 1, wherein said solid transport material includes a hygroscopic solid transport polymer that is selected from the group consisting of poly(acrylic acid), poly(ethylene glycol), poly(2-hydroxyethyl methacrylate), poly(vinyl imidazole), poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), poly(vinylpyrolidone), modified cellulosic polymers, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, and combinations thereof.
 7. The antimicrobial structure of claim 1, wherein said solid transport material includes a hydrophobic, non-lipophobic solid transport polymer that is selected from the group consisting of poly(propylene glycol), poly(tetramethylene glycol), polybutadiene, polycarbonate, polycaprolactone, acrylic polyols, and combinations thereof.
 8. The antimicrobial structure of claim 1, wherein said solid transport material includes a hydrophilic solid transport polymer with ionic charge, and wherein said ionic charge is present within said hydrophilic solid transport polymer as carboxylate groups, amine groups, sulfate groups, or phosphate groups.
 9. The antimicrobial structure of claim 1, wherein said solid transport material includes an electrolyte solid transport polymer that is selected from the group consisting of polyethylene oxide, polypropylene oxide, polycarbonates, polysiloxanes, polyvinylidene difluoride, and combinations thereof.
 10. The antimicrobial structure of claim 1, wherein said solid structural material is a solid structural polymer, wherein said solid transport material is a solid transport polymer, and wherein said solid structural polymer is crosslinked, via a crosslinking molecule, with said solid transport polymer.
 11. The antimicrobial structure of claim 10, wherein said crosslinking molecule includes at least one moiety selected from the group consisting of an amine moiety, a hydroxyl moiety, an isocyanate moiety, and a combination thereof.
 12. The antimicrobial structure of claim 1, wherein said continuous transport phase is a solid solution or solid suspension of said solid transport material and said antimicrobial agent.
 13. The antimicrobial structure of claim 1, wherein said continuous transport phase contains a transport-phase liquid that at least partially dissolves said antimicrobial agent.
 14. The antimicrobial structure of claim 13, wherein said transport-phase liquid is selected from the group consisting of water, dialkyl carbonate, propylene carbonate, γ-butyrolactone, 2-phenoxyethanol, and combinations thereof.
 15. The antimicrobial structure of claim 13, wherein said transport-phase liquid is selected from ionic liquids.
 16. The antimicrobial structure of claim 13, wherein said transport-phase liquid contains one or more water-soluble salts, and wherein optionally at least one of said water-soluble salts functions as said antimicrobial agent.
 17. The antimicrobial structure of claim 16, wherein said water-soluble salts are selected from the group consisting of copper chloride, copper nitrate, zinc chloride, zinc nitrate, silver chloride, silver nitrate, and combinations thereof.
 18. The antimicrobial structure of claim 14, wherein said transport-phase liquid is a eutectic liquid salt, and wherein said eutectic liquid salt is derived from ammonium salts.
 19. The antimicrobial structure of claim 18, wherein said eutectic liquid salt contains said antimicrobial agent.
 20. (canceled)
 21. The antimicrobial structure of claim 1, wherein said antimicrobial agent is selected from quaternary ammonium molecules.
 22. The antimicrobial structure of claim 1, wherein said antimicrobial agent is selected from N-halamines.
 23. The antimicrobial structure of claim 1, wherein said antimicrobial agent is selected from oxidizing molecules, and wherein said oxidizing molecules are selected from the group consisting of sodium hypochlorite, hypochlorous acid, hydrogen peroxide, and combinations thereof.
 24. The antimicrobial structure of claim 1, wherein said antimicrobial agent is selected from metal ions, and wherein said metal ions are selected from the group consisting of silver, copper, zinc, and combinations thereof.
 25. The antimicrobial structure of claim 1, wherein said antimicrobial structure is characterized in that said antimicrobial agent has a diffusion coefficient between 10⁻¹⁶ m²/s and 10⁻⁹ m²/s, measured at 25° C. and 1 bar, within said continuous transport phase.
 26. The antimicrobial structure of claim 1, wherein said antimicrobial structure contains embedded electrodes, and wherein said antimicrobial agent is electrically or electrochemically rechargeable.
 27. The antimicrobial structure of claim 1, wherein said antimicrobial structure further contains one or more protective layers.
 28. The antimicrobial structure of claim 1, wherein said antimicrobial structure is a coating or is present in a coating or is present at a surface of a bulk object.
 29. (canceled)
 30. The antimicrobial structure of claim 1, wherein said electrolyte salt is selected from the group consisting of salts of transition metals, salts of metalloids, salts of alkali metals, salts of alkaline earth metals, and combinations thereof.
 31. The antimicrobial structure of claim 1, wherein said aqueous or non-aqueous solvent is selected from the group consisting of water, alcohols, ethers, esters, ketones, aldehydes, carbonates, sulfoxides, sulfones, nitriles, phosphates, and combinations thereof. 